Intratumoral budding is preoperative biopsies predicts local and distant metastasis in colorectal cancer patients

Objective: In 2011, the term “intratumoral budding, ITB” was used to describe the presence of tumor buds within the main tumor body and was correlated to worse clinical outcome in colorectal cancer patients. Here, we further elucidate the potential clinical role of ITB in pre-operative biopsies using pan-cytokeratin stained tissues and a quantitative scoring system. Method: 139 pre-operative biopsies from patients with colorectal cancer underwent immunohistochemistry for pancytokeratin (AE1/AE3). ITB were counted in the area of densest budding (40×) and classified as high-grade when >10 buds/HPF were observed based on receiver operating characteristic (ROC) curve analysis. Results: High-grade ITB occurred in 26.6 % of cases and was associated with right-sided tumor location (p=0.0356), more advanced pT (p=0.0198) and pN (p<0.0001) classifications, distant metastasis (p=0.0164), higher tumor grade (p=0.0037) and lymphatic invasion (p=0.0445). The specificity and positive predictive value for lymph node metastasis was 86.7 % and 75.6 %, respectively. Disease-free survival was significantly worse in patients with high-grade ITB (5-year survival=25 %) in comparison to patients with low-grade ITB (5-year survival=55 %) (p=0.0157). Conclusion: The assessment of ITB in pre-operative biopsies is predictive of local and distant metastasis in corresponding resections and should be considered in daily management of colorectal cancer patients.

Trust and Social Networks in a Changing Europe.

This project set out to investigate the effects of the recent massive social transitions in Eastern Europe on the everyday social lives of the inhabitants of three very different nations: Georgia, Russia and Hungary. It focused in particular on the availability and nature of the support networks available to three different segments of each of the societies (manual workers, students and entrepreneurs) and the impact of network participation on psychological and physical well-being. The group set four specific questions to investigate: the part played by individual psychological beliefs in the formation and maintenance of social networks and the consequent formation of trusting relations; the implication of the size and quality of these networks for mental health; the nature of the social groups inhabited by the respondents and the implication of their work schedule and daily routines on the maintenance of a social and family life; and an analysis of how cultures vary in their social networks and intimacy. Three different methods were used to examine social support and its implications: structured questionnaires, semi-structured short interviews and a media analysis of newspaper materials. The questionnaires were administered to 150 participants in each country, equally divided between students studying full time, manual workers employed in factories, and business people (small kiosk owners, whose work and life style differs considerably from that of the manual workers). The questionnaires investigated various predictors of social support including the locus of control, relationship beliefs, individualism-collectivism and egalitarianism, demographic variables (age, gender and occupation), social support, both in general and in relation to significant events that have occurred since the transition from communism. Those with an internal locus of control were more likely to report a higher level of social support, as were collectivists, while age too was a significant predictor, with younger respondents enjoying higher levels of support, regardless of the measures of support employed. Respondents across the cultures referred to a decline of social support and the group also found a direct correlation between social support and mental health outcomes. All 450 respondents were interviewed on their general responses to changes in their lives since the fall of communism and the effects of their work lives on their social lives and the home environment. The interviews revealed considerable variations in the way in which work-life offered opportunities for a broader social life and also provided a hindrance to the development of fulfilling relationships. Many of the work experiences discussed were culture specific, with work having a particularly negative impact on the social life of Russian entrepreneurs but being seen much more positively in Georgia. This may reflect the nature of support offered in a society as overall support levels were lowest in Russia, meaning that social support may be of particular importance there. The way in cultural values and norms about personal relationships are transmitted in a culture is a critical issue for social psychologists and the group examined newspaper articles in those newspapers read by the respondents in each of the three countries. These revealed a number of different themes. The concept of a divided society and its implications for personal relationships was clearest in Russian and Hungary, where widely-read newspapers dwelt on the contrast between "new Russians/Hungarians" and the older, poorer ones and extended considerable sympathy to those suffering from neglect in institutions. Magyar Nemzet, a paper widely read by Hungarian students reflects the generally more pessimistic tone about personal relationships in Russia and Hungary and gave a particularly detailed analysis of the implications this holds for human relations in a modern society. In Georgia, however, the tone of the newspapers is more positive, stressing greater social cohesion. Part of this cohesion is framed in the context of religion, with the church appealing to a broader egalitarianism, whereas in less egalitarian Hungary appeals by the Church are centred more on the nuclear family and its need for expansion in both size and influence. The division between the sexes was another prominent issue in Hungary and Russia, while the theme of generational conflict also emerged in Hungarian and Georgian papers, although with some understanding of "young people today". The team's original expectation that the different newspapers read by the different groups of respondents would present differing images of personal relationships was not fulfilled, as despite variations in style, they found little clear "ideological targeting" of any particular readership. They conclude that the vast majority of respondents recognised that the social transition from communism has had a significant impact on the well-being of social relationships and that this is a pertinent issue for all segments of society. While the group see the data collected as a source to be worked on for some time in the future, their initial impressions include the following. Social support is clearly an important concern across all three countries. All respondents (including the students) lament the time taken up by their heavy work schedules and value their social networks and family ties in particular. The level of social support differs across the countries investigated, with Georgian apparently enjoying significantly higher levels of social support. The analysis produced an image of a relatively cohesive and egalitarian society in which even the group most often seen as distant from the general population, business people, is supported by a strong social network. In contrast, the support networks available to the Russian respondents seem particularly weak and reflect a general sense of division and alienation within the culture as a whole. The implications of low levels of social support may vary across countries. While Russians reported the lowest level of mental health problems, the link between social support and mental health may be strongest in that country. In contrast, in Hungary it is the link between fatalism and mental health problems which is particularly strong, while in Georgia the strongest correlation was between mental health and marital quality, emphasising the significance of the marital relationship in that country.

Levocetirizine is an effective treatment in patients suffering from chronic idiopathic urticaria: a randomized, double-blind, placebo-controlled, parallel, multicenter study

BACKGROUND: Chronic idiopathic urticaria (CIU) is defined by the almost daily presence of urticaria for at least 6 weeks without an identifiable cause. Symptoms include short-lived wheals, itching, and erythema. CIU impedes significantly a patient's quality of life (QoL). Levocetirizine is an antihistamine from the latest generation approved for CIU. AIM: To investigate the efficacy of levocetirizine, 5 mg, and placebo for the symptoms and signs of CIU, as well as for the QoL and productivity. METHODS: The primary criteria of evaluation were the pruritus severity scores over 1 week of treatment and over 4 weeks. The QoL was assessed via the Dermatology Life Quality Index (DLQI). RESULTS: Baseline pruritus severity scores were comparable in the two treatment groups (2.06+/-0.58). After 1 week, levocetirizine was superior to placebo and demonstrated a considerable efficacy (difference=0.78, P<0.001). This efficacy was maintained over the entire study period (4 weeks, P<0.001). The number and size of wheals were considerably reduced compared with placebo over 1 week and over the total treatment period (P

Pathological baroreceptor sensitivity in patients suffering from somatization disorders: do they correlate with symptoms?

We conducted a study to investigate whether patients with somatization disorders (ICD-10, F45.0) show abnormal values in autonomic testing.

MET Y1253D-activating point mutation and development of distant metastasis in advanced head and neck cancers

We investigated if the MET-activating point mutation Y1253D influences clinical outcomes in patients with advanced squamous cell carcinoma of the head and neck (HNSCC). The study population consisted of 152 HNSCC patients treated by hyperfractionated radiotherapy alone or concomitant with chemotherapy between September 1994 and July 2000. Tumors were screened for the presence of the MET-activating point mutation Y1253D. Seventy-eight patients (51%) received radiotherapy alone, 74 patients (49%) underwent radiotherapy concomitant with chemotherapy. Median patient age was 54 years and median follow-up was 5.5 years. Distant metastasis-free survival, local relapse-free survival and overall survival were compared with MET Y1253D status. During follow-up, 29 (19%) patients developed distant metastasis. MET Y1253D was detected in tumors of 21 out of 152 patients (14%). Distant metastasis-free survival (P = 0.008) was associated with MET Y1253D. In a multivariate Cox regression model, adjusted for T-category, only presence of MET Y1253D was associated with decreased distant metastasis-free survival: hazard ratio = 2.5 (95% confidence interval: 1.1, 5.8). The observed association between MET Y1253D-activating point mutation and decreased distant metastasis-free survival in advanced HNSCC suggests that MET may be a potential target for specific treatment interventions.

PET-CT-guided interventions in the management of FDG-positive lesions in patients suffering from solid malignancies: initial experiences

Positron emission tomography-computed tomography (PET-CT) has gained widespread acceptance as a staging investigation in the diagnostic workup of malignant tumours and may be used to visualize metabolic changes before the evolution of morphological changes. To make histology of PET findings without distinctive structural changes available for treatment decisions, we developed a protocol for multimodal image-guided interventions using an integrated PET-CT machine. We report our first experience in 12 patients admitted for staging and restaging of breast cancer, non-small cell lung cancer, cervical cancer, soft tissue sarcoma, and osteosarcoma. Patients were repositioned according to the findings in PET-CT and intervention was planned based on a subsequent single-bed PET-CT acquisition of the region concerned. The needle was introduced under CT guidance in a step-by-step technique and correct needle position in the centre of the FDG avid lesion was assured by repetition of a single-bed PET-CT acquisition before sampling. The metabolically active part of lesions was accurately targeted in all patients and representative samples were obtained in 92%. No major adverse effects occurred. We conclude that PET-CT guidance for interventions is feasible and may be promising to optimize the diagnostic yield of CT-guided interventions and to make metabolically active lesions without morphological correlate accessible to percutaneous interventions.